Successful Latissimus Dorsi Free Flap Salvage using Intraoperative Vasopressors: A Case Report

Arterial thrombosis is a rare, but dreadful complication in microvascular surgery. Here we report on a case of recurrent arterial thrombosis in a latissimus dorsi (LD) free flap used for scalp reconstruction in an 18-year-old woman who sustained a gunshot wound (GSW) to the head. In the immediate postoperative period, internal and external doppler signals to the flap were lost. Emergent surgical exploration revealed arterial thrombosis, which was emergently explored and successfully repaired. Doppler signals were again lost and the flap was emergently explored for a second time. Following revision of the arterial anastomosis, flap perfusion decreased and appeared to correlate with the patient’s blood pressure. After administration of vasopressors to increase the Mean Arterial Pressure (MAP) to a goal of 70 or greater, flap perfusion and doppler signals were consistent. Here we describe a case of successful free flap salvage using both intraoperative and postoperative vasopressors for recurrent arterial thrombosis. Furthermore, vasopressor administration may be beneficial in select patients to maintain adequate flap perfusion in those who demonstrate intraoperative hypotension and no other identifiable causes of flap compromise, as in the present case

Chemotherapy vs supportive care alone for relapsed gastric, gastroesophageal junction, and oesophageal adenocarcinoma: a meta-analysis of patient-level data.

BACKGROUND: Second-line chemotherapy treatment of patients with relapsed gastric and oesophageal cancers in comparison with supportive care (SC) alone has been supported by recent phase 3 clinical trials, but a meta-analysis of patient-level data is lacking. METHODS: We searched Medline, the Cochrane Central Register of Controlled Trials (CENTRAL), and the Web of Science for phase 3 clinical trials that compared second-line chemotherapy with SC alone for gastric and oesophageal cancers. A meta-analysis of the comprehensive patient-level data from the three identified trials was performed. RESULTS: A total of 410 patients with gastric (n=301), gastroesophageal junction (n=76), or oesophageal (n=33) adenocarcinoma were identified. In all, 154 patients received single-agent docetaxel and 84 patients received single-agent irinotecan, each with SC. SC alone was given to 172 patients. Chemotherapy significantly reduced the risk of death (hazard ratio (HR)=0.63, 95% confidence interval (CI)=0.51-0.77, P<0.0001). This effect was observed for treatment with docetaxel (HR=0.71, 95% CI=0.56-0.89, P=0.003) and irinotecan (HR=0.49, 95% CI=0.36-0.67, P<0.001). Overall survival (OS) benefit was greatest for patients who progressed 3-6 months following first-line chemotherapy (HR=0.39, 95% CI=0.26-0.59, P<0.0001). Performance status (PS) 0-1 compared with PS 2 (HR=0.66, 95% CI=0.46-0.94, P=0.02), locally advanced disease compared with metastatic disease (HR=0.41, 95% CI=0.25-0.67, P=0.0004) and older age (HR=0.94 per 5 years, 95% CI=0.90-0.99, P=0.01) were significant predictors of improved OS. Progression of disease during first-line treatment (HR=1.24, 95% CI=0.96-1.59) or within the first 3 months of completion of first-line treatment (HR=1.42, 95% CI=1.09-1.83) were predictors of an increased risk of death compared with progression between 3 and 6 months (P=0.03). Health-related quality of life outcomes were reported in only one of the three trials, precluding meta-analysis of these parameters. CONCLUSIONS: This meta-analysis of patient-level data confirms that second-line chemotherapy treatment results in significantly better OS compared with SC alone in patients with platinum and fluoropyrimidine refractory gastric and oesphageal adenocarcinoma. Health-related quality of life outcomes should be included in future trials in this setting.TJ and CC were supported by the Wellcome Trust Translational Medicine and Therapeutics programme and the National Institute for Health Research.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/bjc.2015.45

Molecular effects of Lapatinib in the treatment of HER2 overexpressing oesophago-gastric adenocarcinoma.

BACKGROUND: Lapatinib, a dual EGFR and HER2 inhibitor has shown disappointing results in clinical trials of metastatic oesophago-gastric adenocarcinomas (OGAs), and in vitro studies suggest that MET, IGFR, and HER3 confer resistance. This trial applied Lapatinib in the curative neoadjuvant setting and investigated the feasibility and utility of additional endoscopy and biopsy for assessment of resistance mechanisms ex vivo and in vivo. METHODS: Patients with HER2 overexpressing OGA were treated for 10 days with Lapatinib monotherapy, and then in combination with three cycles of Oxaliplatin and Capecitabine before surgery. Endoscopic samples were taken for molecular analysis at: baseline including for ex vivo culture +/- Lapatinib to predict in vivo response, post-Lapatinib monotherapy and at surgery. Immunohistochemistry (IHC) and proteomic analysis was performed to assess cell kinetics and signalling activity. RESULTS: The trial closed early (n=10) due to an anastomotic leak in two patients for which a causative effect of Lapatinib could not be excluded. The reduction in Phosphorylated-HER2 (P-HER2) and P-EGFR in the ex vivo-treated biopsy demonstrated good correlation with the in vivo response at day 10. Proteomic analysis pre and post-Lapatinib demonstrated target inhibition (P-ERBB2, P-EGFR, P-PI3K, P-AKT, and P-ERK) that persisted until surgery. There was also significant correlation between the activation of MET with the level of P-Erk (P=0.0005) and P-PI3K : T-PI3K (total PI3K) ratio (P=0.0037). There was no significant correlation between the activation status of IGFR and HER3 with downstream signalling molecules. CONCLUSIONS: Additional endoscopy and biopsy sampling for multiple biomarker endpoints was feasible and confirmed in vitro data that MET is likely to be a significant mechanism of Lapatinib resistance in vivo.This research was funded by the Medical Research Council [Grant SK002].This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/bjc.2015.34

Sound-driven single-electron transfer in a circuit of coupled quantum rails

Abstract: Surface acoustic waves (SAWs) strongly modulate the shallow electric potential in piezoelectric materials. In semiconductor heterostructures such as GaAs/AlGaAs, SAWs can thus be employed to transfer individual electrons between distant quantum dots. This transfer mechanism makes SAW technologies a promising candidate to convey quantum information through a circuit of quantum logic gates. Here we present two essential building blocks of such a SAW-driven quantum circuit. First, we implement a directional coupler allowing to partition a flying electron arbitrarily into two paths of transportation. Second, we demonstrate a triggered single-electron source enabling synchronisation of the SAW-driven sending process. Exceeding a single-shot transfer efficiency of 99%, we show that a SAW-driven integrated circuit is feasible with single electrons on a large scale. Our results pave the way to perform quantum logic operations with flying electron qubits

Releasing incompatible males drives strong suppression across populations of wild and Wolbachia-carrying Aedes aegypti in Australia

Releasing sterile or incompatible male insects is a proven method of population management in agricultural systems with the potential to revolutionize mosquito control. Through a collaborative venture with the “Debug” Verily Life Sciences team, we assessed the incompatible insect technique (IIT) with the mosquito vector Aedes aegypti in northern Australia in a replicated treatment control field trial. Backcrossing a US strain of Ae. aegypti carrying Wolbachia wAlbB from Aedes albopictus with a local strain, we generated a wAlbB2-F4 strain incompatible with both the wild-type (no Wolbachia) and wMel-Wolbachia Ae. aegypti now extant in North Queensland. The wAlbB2-F4 strain was manually mass reared with males separated from females using Verily sex-sorting technologies to obtain no detectable female contamination in the field. With community consent, we delivered a total of three million IIT males into three isolated landscapes of over 200 houses each, releasing ∼50 males per house three times a week over 20 wk. Detecting initial overflooding ratios of between 5:1 and 10:1, strong population declines well beyond 80% were detected across all treatment landscapes when compared to controls. Monitoring through the following season to observe the ongoing effect saw one treatment landscape devoid of adult Ae. aegypti early in the season. A second landscape showed reduced adults, and the third recovered fully. These encouraging results in suppressing both wild-type and wMel-Ae. aegypti confirms the utility of bidirectional incompatibility in the field setting, show the IIT to be robust, and indicate that the removal of this arbovirus vector from human-occupied landscapes may be achievable

Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers.

Germline CDH1 mutations confer a high lifetime risk of developing diffuse gastric (DGC) and lobular breast cancer (LBC). A multidisciplinary workshop was organised to discuss genetic testing, surgery, surveillance strategies, pathology reporting and the patient's perspective on multiple aspects, including diet post gastrectomy. The updated guidelines include revised CDH1 testing criteria (taking into account first-degree and second-degree relatives): (1) families with two or more patients with gastric cancer at any age, one confirmed DGC; (2) individuals with DGC before the age of 40 and (3) families with diagnoses of both DGC and LBC (one diagnosis before the age of 50). Additionally, CDH1 testing could be considered in patients with bilateral or familial LBC before the age of 50, patients with DGC and cleft lip/palate, and those with precursor lesions for signet ring cell carcinoma. Given the high mortality associated with invasive disease, prophylactic total gastrectomy at a centre of expertise is advised for individuals with pathogenic CDH1 mutations. Breast cancer surveillance with annual breast MRI starting at age 30 for women with a CDH1 mutation is recommended. Standardised endoscopic surveillance in experienced centres is recommended for those opting not to have gastrectomy at the current time, those with CDH1 variants of uncertain significance and those that fulfil hereditary DGC criteria without germline CDH1 mutations. Expert histopathological confirmation of (early) signet ring cell carcinoma is recommended. The impact of gastrectomy and mastectomy should not be underestimated; these can have severe consequences on a psychological, physiological and metabolic level. Nutritional problems should be carefully monitored

250 labels used to stigmatise people with mental illness

<p>Abstract</p> <p>Background</p> <p>The stigma against people with mental illness is a major barrier to help-seeking in young people for mental health problems. The objective of this study was to investigate the extent of stigma in relation to treatment avoidance in 14 year-old school students in England in relation to how they refer to people with mental illness.</p> <p>Methods</p> <p>This is a qualitative, cross-sectional study. The data were gathered as part of the baseline assessment for an intervention study intended to reduce stigma among 14 year old school students. The participating schools were two grammar (selective) schools and three comprehensive (non-selective) schools. At the start of the lesson, the students were asked 'What sorts of words or phrases might you use to describe someone who experiences mental health problems?' Words and terms used to refer to mental illness were enumerated. Using the grounded theory approach, words and terms were grouped in terms of their denotative and connotative meanings. Labels were then derived to capture the key themes attached by the students to the concepts of mental illness. The frequencies of occurrence for each word were also tabulated.</p> <p>Results</p> <p>400 of the 472 participating students (85%) provided 250 words and terms to describe a person with mental illness. Five themes were identified from the data. The first theme called 'popular derogatory terms' (116 items) accounted for nearly half of the words examined. The second theme occurred less often and was described as 'negative emotional state' (61 items). The third theme demonstrated the confusion of young people between physical disabilities, learning difficulties and mental health problems (38 items). The use of psychiatric diagnoses (15 items) and terms related to violence (9 items) were unexpectedly uncommon.</p> <p>Conclusion</p> <p>Our findings suggest the hypothesis that help-seeking by mentally ill young people may be improved by interventions that address both their lack of factual information about mental illness, and those which reduce their strong negative emotional reactions towards people with mental illness.</p